Ceftriaxone as Home IV for Staph Infections

NCT04141787 | Unknown Phase 4

• 1 other identifier: C2018-018
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 2

Brief Summary

Patients who are admitted to hospital with serious infections, such as those in bone, joints or spine, require a long course of intravenous (IV) antibiotics. After an initial treatment course in hospital or through a dedicated outpatient antibiotic program many patients can complete their treatment course at home. Such infections are often caused by bacteria called Staphylococci, and currently there are three antibiotic options used routinely. A fourth antibiotic, ceftriaxone, is a promising alternative; it is also effective against Staphylococci, and is more convenient, less costly and easier to give at home, however, it has not been studied thoroughly in a prospective manner. This study will compare ceftriaxone to routinely used antibiotics (cloxacillin, cefazolin or daptomycin) to see if ceftriaxone is equally as safe and efficacious in curing deep-seated Staphylococcal infections in patients receiving home IV antibiotics. Patients with deep-seated infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) or coagulase-negative Staphylococcal species will be randomly assigned home IV treatment with ceftriaxone OR one of the three other antibiotics before leaving the hospital. Patients will then receive usual care from an Infectious Disease physician and Home IV team. The study team will assess whether cure has been achieved by the end of the IV treatment, follow-up at 6 months to see if patients remain infection-free, and record any side-effects of treatment. The overall goal is to determine whether ceftriaxone can be considered non-inferior to usual antibiotic treatment in treating Staphylococcal infections in a home IV setting.

Conditions

Staphylococcal Infections; Osteomyelitis; CNS Infection; Septic Arthritis; Diabetic Foot Infection; Vertebral Osteomyelitis; Abscess; Coagulase Negative Staphylococcal Infection

Keywords

Ceftriaxone; Deep-seated Infections; Staphylococcus aureus; Coagulase-negative Staphylococcus species; MSSA; CoNS

Outcome Measures

Primary Outcomes (1)

• Clinical cure rate of deep-seated methicillin sensitive Staphylococcal infections

  Clinical cure of deep-seated MSSA and CoNS infections will be defined by improvement in clinical parameters, imaging findings and laboratory values at the time of completion of a pre-specified duration of antibiotic treatment based on infection site and clinical guidelines. Clinical cure defined by treating infectious diseases clinicians based on composite of: * Resolution of signs and symptoms of deep-seated infection * Improvement in inflammatory markers; defined as a C-reactive protein (CRP) less than 50% of initial CRP value * Improvement in follow- up imaging when conducted, as determined by the interpreting radiologist

  Up to 6 months post-randomization

Secondary Outcomes (2)

• Treatment failure at six months post-randomization

  At six months following randomization

• Adverse event rate

  Up to 6 months post-randomization

Other Outcomes (2)

• Rate of antibiotic substitution or discontinuation

  Up to 6 months post-randomization

• Duration of therapy

  Up to 6 months post-randomization

Study Arms (2)

Ceftriaxone

ACTIVE COMPARATOR

Ceftriaxone 2g IV q24hvia Gravity (or q12h in the case of CNS infections) Duration dependent on site of infection, determined by treating infectious diseases (ID) clinicians based on accepted clinical guidelines.

Drug: Ceftriaxone

Usual Antibiotics (Cloxacillin, Cefazolin, Daptomycin)

ACTIVE COMPARATOR

"Usual Antibiotics" to treat methicillin-susceptible Staphylococcal infections * Cloxacillin 2g IV q4h via Pump (dose adjusted for renal function) * Cefazolin 2g IV q8h via Preloaded Syringe (dose adjusted for renal function) * Daptomycin 6-10mg/kg IV daily via Gravity (dose will be determined based on the severity of infection as per discretion of the ID clinician and in accordance with most recent evidence) * Duration dependent on site of infection, determined by treating infectious diseases clinicians based on accepted clinical guidelines.

Drug: Usual Antibiotics (Cloxacillin, Cefazolin, Daptomycin)

Interventions

Ceftriaxone DRUG

Participants with methicillin-sensitive deep-seated staphylococcal infections eligible for treatment on home IV will be randomly assigned to a "treatment" group of ceftriaxone or "standard therapy/usual antibiotics" with either cloxacillin, cefazolin or daptomycin. The treatment with one of the three "standard therapies/usual antibiotics" will be left to the discretion of the treating Infectious Disease doctor, in line with current standards of practice.

Also known as: Rocephin

Ceftriaxone

Usual Antibiotics (Cloxacillin, Cefazolin, Daptomycin) DRUG

Participants with methicillin-sensitive deep-seated staphylococcal infections eligible for treatment on home IV will be randomly assigned to a "treatment" group of ceftriaxone or "standard therapy/usual antibiotics" with either cloxacillin, cefazolin or daptomycin. The treatment with one of the three "standard therapies/usual antibiotics" will be left to the discretion of the treating Infectious Disease doctor, in line with current standards of practice.

Also known as: Cloxacillin, Cefazolin, Daptomycin, Ancef, Cubicin

Usual Antibiotics (Cloxacillin, Cefazolin, Daptomycin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• are 18 years of age or older
• were referred to and assessed by an Infectious Disease physician in the form of a clinical consult as either:
• an inpatient at the Royal Jubilee or Victoria General Hospitals
• an outpatient at the emergency department of one of the aforementioned hospitals
• an outpatient at the Outpatient Parenteral Antibiotic Therapy (OPAT) clinic
• have a clinically and/or radiographically diagnosed deep-seated MSSA or coagulase-negative Staphylococcal infection as defined in Table 1 of the protocol (Osteomyelitis, Discitis/Epidural abscess, Central Nervous System (CNS) infection, Abscess, Septic Arthritis (including Prosthetic Joint Infection), Diabetic foot infection) and the diagnosis has been made or confirmed by the Infectious Disease physician
• have had the causative pathogen confirmed microbiologically as either MSSA or CoNS through a laboratory sample indicative of the current site of infection
• are deemed to require prolonged IV antibiotic therapy and subsequently referred for assessment by the home IV program by the Infectious Disease physician
• are an appropriate candidate for the home IV program as determined by the assessing Home IV nurse, and are eligible for treatment with BOTH ceftriaxone AND at least one of the usual alternatives, namely cloxacillin, cefazolin or daptomycin
• provide written informed consent to participate in the study
• have their culture and sensitivity results finalized prior to randomization, with the isolate confirmed to be sensitive to all study drugs (susceptibilities are discussed in the "Microbiological Testing" section of the protocol)
• are successfully randomized to either ceftriaxone OR one of cloxacillin, cefazolin or daptomycin before Home IV orders are written (the choice between the three comparator antibiotics will be at the discretion of the treating Infectious Disease physician)
• receive at least one dose of the antibiotic to which they were randomized prior to being discharged on the home IV program
• are physically discharged to the home IV program for any duration

You may not qualify if:

• younger than 18 years of age
• pregnant
• involved in another therapeutic trial
• are not under the care of an Infectious Disease physician
• are unable to provide informed consent due to language or cognitive barriers
• are not appropriate for Home IV therapy as determined by the assessing Home IV nurse
• are concurrently receiving other anti-staphylococcal antibiotics (excluding the synergistic use of rifampin for prosthetic joint infections) at the time of discharge on the home IV program
• have relevant cultures indicating a polymicrobial infection (except in the case of diabetic foot infections where they may be included if MSSA or CoNS is determined to be the dominant pathogen by the Infectious Disease physician and any additional antibiotics used do not exhibit activity against MSSA or CoNS)
• have concurrent or incompletely treated bacteremia with MSSA or CoNS (as defined in protocol)
• have infective endocarditis based on imaging or clinical judgement
• are receiving home IV antibiotics solely as palliative therapy
• are unable to tolerate ceftriaxone AND any ONE of the standardly used antibiotics (cloxacillin, cefazolin, daptomycin) because of an allergy or intolerance

Sponsors & Collaborators

• Vancouver Island Health Authority: lead

Study Sites (2)

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

RECRUITING

Victoria General Hospital

Victoria, British Columbia, V8Z 6R5, Canada

RECRUITING

Related Publications (5)

• Lother SA, Press N. Once-Daily Treatments for Methicillin-Susceptible Staphylococcus aureus Bacteremia: Are They Good Enough? Curr Infect Dis Rep. 2017 Sep 23;19(11):43. doi: 10.1007/s11908-017-0599-0.

  PMID: 28942574 BACKGROUND

• Hotchkies L, Grima DT, Hedayati S. The total process cost of parenteral antibiotic therapy: beyond drug acquisition cost. Clin Ther. 1996 Jul-Aug;18(4):716-25; discussion 702. doi: 10.1016/s0149-2918(96)80222-0.

  PMID: 8879899 BACKGROUND

• Patel UC, McKissic EL, Kasper D, Lentino JR, Pachucki CT, Lee T, Lopansri BK. Outcomes of ceftriaxone use compared to standard of therapy in methicillin susceptible staphylococcal aureus (MSSA) bloodstream infections. Int J Clin Pharm. 2014 Dec;36(6):1282-9. doi: 10.1007/s11096-014-9999-5. Epub 2014 Sep 4.

  PMID: 25186790 BACKGROUND

• Wieland BW, Marcantoni JR, Bommarito KM, Warren DK, Marschall J. A retrospective comparison of ceftriaxone versus oxacillin for osteoarticular infections due to methicillin-susceptible Staphylococcus aureus. Clin Infect Dis. 2012 Mar 1;54(5):585-90. doi: 10.1093/cid/cir857. Epub 2011 Dec 5.

  PMID: 22144536 BACKGROUND

• Winans SA, Luce AM, Hasbun R. Outpatient parenteral antimicrobial therapy for the treatment of methicillin-susceptible Staphylococcus aureus: a comparison of cefazolin and ceftriaxone. Infection. 2013 Aug;41(4):769-74. doi: 10.1007/s15010-013-0477-0. Epub 2013 May 19.

  PMID: 23686435 BACKGROUND

MeSH Terms

Conditions

Staphylococcal Infections; Osteomyelitis; Central Nervous System Infections; Arthritis, Infectious; Abscess

Interventions

Ceftriaxone; Cloxacillin; Cefazolin; Daptomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Bone Diseases, Infectious; Bone Diseases; Musculoskeletal Diseases; Central Nervous System Diseases; Nervous System Diseases; Arthritis; Joint Diseases; Suppuration; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Oxacillin; Penicillins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Eric Partlow, MD, FRCPC

  Vancouver Island Health Authority

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Partlow, MD, FRCPC

CONTACT

778-404-0144; eric.partlow@viha.ca

Jolanta Piszczek, Pharm D, MSc

CONTACT

250-589-8507; jolanta.piszczek@viha.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Infectious Diseases Physician (Section Chief)

Model Details: This is a prospective, randomized, unblinded non-inferiority trial being led by infectious diseases clinicians. We have chosen a pragmatic trial design which represents the most efficient use of available resources to test the study hypothesis and is the designed to determine effectiveness as opposed to efficacy.

Study Record Dates

• First Submitted: October 17, 2019
• First Posted: October 28, 2019
• Study Start: July 11, 2019
• Primary Completion: July 1, 2023
• Study Completion: March 30, 2024
• Last Updated: October 28, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 6 months following study completion.
• Access Criteria: Access requests will be assessed by a review panel associated with Vancouver Island Health Authority.

Locations

CA (2)